Vitamin D derivatives with cyclic substructures in the side chains, process and intermediate products for their production, and the use for the production of pharmaceutical agents

• US 7,115,758 B2
• Filed: 11/26/2002
• Issued: 10/03/2006
• Est. Priority Date: 07/23/1999
• Status: Expired due to Fees

• Current Assignee: Schering Ag (Merck & Co., Inc.)
• Original Assignee: Schering Ag (Merck & Co., Inc.)
• Inventors: Fähnrich, Marianne, Giesen, Claudia, Haberey, Martin, Steinmeyer, Andreas, Schwarz, Katica
• Primary Examiner(s): QAZI, SABIHA NAIM
• Application Number:
  US10/303,916
• Publication Number:
  US 20030149006A1
• Time in Patent Office: 1,407 Days
• Field of Search: 552/653, 514/167, 514/438, 514/439, 514/461, 514/471, 540/200, 540/202, 548/237, 548/239
• US Class Current: 552/653
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/04 Antipruritics
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 17/14 for baldness or alopecia
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 3/14 for calcium homeostasis vitamin D A61P3/02; parathyroid hormones A61P5/18; calcitonin A61P5/22; osteoporosis A61P19/10; bone metastasis A61P35/04
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: B21C 25/02 : Dies
• CPC Class Codes: B21C 25/10 : Making tools by operations not covered by a single other subclass
• CPC Class Codes: C07C 401/00 : Irradiation products of cholesterol or its derivatives; Vitamin D derivatives, 9,10-seco cyclopenta[a]phenanthrene or analogues obtained by chemical preparation without irradiation
• CPC Class Codes: C07D 235/12 : Radicals substituted by oxygen atoms
• CPC Class Codes: C07D 263/32 : with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 277/24 : Radicals substituted by oxygen atoms
• CPC Class Codes: C07D 307/80 : Radicals substituted by oxygen atoms
• CPC Class Codes: C07D 333/16 : by oxygen atoms
• CPC Class Codes: C07D 333/22 : Radicals substituted by doubly bound hetero atoms, or by two hetero atoms other than halogen singly bound to the same carbon atom
• CPC Class Codes: Y02P 20/55 : Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Abstract

The invention relates to vitamin D derivatives of general formula I,

process for their production, intermediate products of the process as well as the use for the production of pharmaceutical agents.

Claims

1. A compound formula I,

2. A compound according to claim 1, in which

R₃ or R₄ is hydrogen,

X₁ and X₂ together are a carbonyl group,

or X₁ is a hydroxyl group or a fluorine atom and X₂ is a hydrogen atom,

or X₁ a hydrogen atom and X₂ means is a hydroxyl group or a fluorine atom,

or X₁ is an —

OC(O)R₅ group and X₂ is a hydrogen atom,

or X₁ is a hydrogen atom and X₂ is an —

OC(O)R₅ group, and

Z is oxazolyl, thiazolyl, or benzothiazolyl, which in each case is unsubstituted or substituted by one or more fluorine, chlorine, bromine or iodine atoms, one or more hydroxy groups, one or more COOR₆ groups, and/or one or more C₁–

C₅ alkyl groups, which in turn can be substituted by one or more fluorine, chlorine, bromine or iodine atoms, C₁–

C₆ alkoxy groups and/or COOR₆ groups.

3. A compound according to claim 1, in which the stereochemistry in 20-position is in the unnatural 20-epi-configuration.

4. A compound according to claim 1, wherein said compound is selected from:

(7E)-(1R,3R,24aR)-24a-(oxazole-4-yl)-24a-homo-19-nor-9,10-secochola-5,7-diene-1,3,24a-triol

(7E)-(1R,3R,24aS)-24a-(oxazole-4-yl)-24a-homo-19-nor-9,10-secochola-5,7-diene-1,3,24a-triol

(5Z,7E)-(1S,3R,24aR)-24a-(oxazole-4-yl)-24a-homo-9,10-secochola-5,7,10(19)-triene-1,3,24a-triol

(5Z,7E)-(1S,3R,24aS)-24a-(oxazole-4-yl)-24a-homo-9,10-secochola-5,7,10(19)-triene-1,3,24a-triol

(7E)-(1R,3R,24aR)-24a-(thiazole-2-yl)-24a-homo-19-nor-9,10-secochola-5,7-diene-1,3,24a-triol

(7E)-(1R,3R,24aS)-24a-(thiazole-2-yl)-24a-homo-19-nor-9,10-secochola-5,7-diene-1,3,24a-triol

(7E)-(1R,3R)-1,3-dihydroxy-24a-(thiazole-2-yl)-24-a-homo-19-nor-9,10-secochola-5,7-dien-24a-one

(5Z,7E)-(1S,3R,24aR)-24a-(thiazole-2-yl)-24a-homo-9,10-secochola-5,7,10(19)-triene-1,3,24a-triol

(5Z,7E)-(1S,3R,24aS)-24a-(thiazole-2-yl)-24a-homo-9,10-secochola-5,7,10(19)-triene-1,3,24a-triol

(5Z,7E)-(1S,3R)-1,3-dihydroxy-24a-(thiazole-2-yl)-24a-homo-9,10-secochola-5,7,10(19)-trien-24a-one

(7E)-(1R,3R,24aR)-24a-(4-methylthiazole-2-yl)-24a-homo-19-nor-9,10-secochola-5,7-diene-1,3,24a-triol

(7E)-(1R,3R,24aS)-24a-(4-methylthiazole-2-yl)-24a-homo-19-nor-9,10-secochola-5,7-diene-1,3,24a-triol

(7E)-(1R,3R)-1,3-dihydroxy-24a-(4-methylthiazole-2-yl)-24a-homo-19-nor-9,10-secochola-5,7-dien-24a-one

(5Z,7E)-(1S,3R,24aR)-24a-(4-methylthiazole-2-yl)-24a-homo-9,10-secochola-5,7,10(19)-triene-1,3,24a-triol

(5Z,7E)-(1S,3R,24aS)-24a-(4-methylthiazole-2-yl)-24a-homo-9,10-secochola-5,7,10(19)-triene-1,3,24a-triol

(5Z,7E)-(1S,3R)-1,3-dihydroxy-24a-(4-methylthiazole-2-yl)-24a-homo-9,10-secochola-5,7,10(19)-trien-24a-one

(7E)-(1R,3R,24aR)-24a-[5-(2-hydroxyethyl)-4-methylthiazole-2-yl]-24a-homo-19-nor-9,10-secochola-5,7-diene-1,3,24a-triol

(7E)-(1R,3R,24aS)-24a-[5-(2-hydroxyethyl)-4-methylthiazole-2-yl]-24a-homo-19-nor-9,10-secochola-5,7-diene-1,3,24a-triol

(7E)-(1R,3R)-1,3-dihydroxy-24a-[5-(2-hydroxyethyl)-4-methylthiazole-2-yl]-24a-homo-19-nor-9,10-secochola-5,7-dien-24a-one

(7E)-(1R,3R,24aR)-24a-(benzothiazole-2-yl)-24a-homo-19-nor-9,10-secochola-5,7-diene-1,3,24a-triol

(7E)-(1R,3R,24aS)-24a-(benzothiazole-2-yl)-24a-homo-19-nor-9,10-secochola-5,7-diene-1,3,24a-triol

(7E)-(1R,3R)-24a-(benzothiazole-2-yl)-1,3-dihydroxy-24a-homo-19-nor-9,10-secochola-5,7-dien-24a-one

(7E)-(1R,3R,20S,24aR)-24a-(thiazole-2-yl)-24a-homo-19-nor-9,10-secochola-5,7-diene-1,3,24a-triol

(7E)-(1R,3R,20S,24aS)-24a-(thiazole-2-yl)-24-a-homo-19-nor-9,10-secochola-5,7-diene-1,3,24a-triol

(7E)-(1R,3R,20S)-1,3-dihydroxy-24a-(thiazole-2-yl)-24-a-homo-19-nor-9,10-secochola-5,7-dien-24a-one

(5Z,7E)-(1S,3R,20S,24aR)-24a-(thiazole-2-yl)-24a-homo-9,10-secochola-5,7,10(19)-triene-1,3,24a-triol

(5Z,7E)-(1S,3R,20S,24aS)-24a-(thiazole-2-yl)-24a-homo-9,10-secochola-5,7,10(19)-triene-1,3,24a-triol

(5Z,7E)-(1S,3R,20S)-1,3-dihydroxy-24a-(thiazole-2-yl)-24a-homo-9,10-secochola-5,7,10(19)-trien-24a-one

(5Z,7E)-(1S,3R,24S)-24-(thiazole-2-yl)-9,10-secochola-5,7,10(19)-triene-1,3,24-triol

(5Z,7E)-(1S,3R,24R)-24-(thiazole-2-yl)-9,10-secochola-5,7,10(19)-triene-1,3,24-triol

(5Z,7E)-(1S,3R)-1,3-dihydroxy-24-(thiazole-2-yl)-9,10-secochola-5,7,10(19)-trien-24-one

(7E)-(1R,3R,20S,24aR)-24a-(oxazole-4-yl)-24a-homo-19-nor-9,10-secochola-5,7-diene-1,3,24a-triol

(7E)-(1R,3R,20S,24aS)-24a-(oxazole-4-yl)-24-a-homo-19-nor-9,10-secochola-5,7-diene-1,3,24a-triol

(7E)-(1R,3R,20S)-1,3-dihydroxy-24a-(oxazole-4-yl)-24-a-homo-19-nor-9,10-secochola-5,7-dien-24a-one

(5Z,7E)-(1S,3R,2,0S,24aR)-24a-(oxazole-4-yl)-24a-homo-9,10-secochola-5,7,10(19)-triene-1,3,24a-triol

(5Z,7E)-(1S,3R,20S,24aS)-24a-(oxazole-4-yl)-24a-homo-9,10-secochola-5,7,10(19)-triene-1,3,24a-triol

(5Z,7E)-(1S,3R,20S)-1,3-dihydroxy-24a-(oxazole-4-yl)-24a-homo-9,10-secochola-5,7,10(19)-trien-24a-one

(5Z,7E)-(1S,3R,24R)-24-(oxazole-4-yl)-9,10-secochola-5,7,10(19)-triene-1,3,24a-triol

(5Z,7E)-(1S,3R,24S)-24-(oxazole-4-yl)-9,10-secochola-5,7,10(19)-triene-1,3,24a-triol

(5Z,7E)-(1S,3R)-1,3-dihydroxy-24-(oxazole-4-yl)-9,10-secochola-5,7,10(19)-trien-24-one

(7E)-(1R,3R,20S,24aR)-24a-(4-methylthiazole-2-yl)-24a-homo-19-nor-9,10-secochola-5,7-diene-1,3,24a-triol

(7E)-(1R,3R,20S,24aS)-24a-(4-methylthiazole-2-yl)-24-a-homo-19-nor-9,10-secochola-5,7-diene-1,3,24a-triol

(7E)-(1R,3R,20S)-1,3-dihydroxy-24a-(4-methylthiazole-2-yl)-24-a-homo-19-nor-9,10-secochola-5,7-dien-24a-one

(5Z,7E)-(1S,3R,20S,24aR)-24a-(4-methylthiazole-2-yl)-24a-homo-9,10-secochola-5,7,10(19)-triene-1,3,24a-triol

(5Z,7E)-(1S,3R,20S,24aS)-24a-(4-methylthiazole-2-yl)-24a-homo-9,10-secochola-5,7,10(19)-triene-1,3,24a-triol

(5Z,7E)-(1S,3R,20S)-1,3-dihydroxy-24a-(4-methylthiazole-2-yl)-24a-homo-9,10-secochola-5,7,10(19)-trien-24a-one

(5Z,7E)-(1S,3R,24R)-24-(4-methylthiazole-2-yl)-9,10-secochola-5,7,10(19)-triene-1,3,24a-triol

(5Z,7E)-(1S,3R,24S)-24-(4-methylthiazole-2-yl)-9,10-secochola-5,7,10(19)-triene-1,3,24a-triol

(5Z,7E)-(1S,3R)-1,3-dihydroxy-24-(4-methylthiazole-2-yl)-9,10-secochola-5,7,10(19)-trien-24-one

(5Z,7E)-(1S,3R,24S)-24-(4-methylthiazole-2-yl)-9,10-secochola-5,7,10(19)-triene-1,3,24-triol

(5Z,7E)-(1S,3R,24R)-24-(4-methylthiazole-2-yl)-9,10-secochola-5,7,10(19)-triene-1,3,24-triol

(5Z,7E)-(1S,3R)-1,3-dihydroxy-24-(4-methylthiazole-2-yl)-9,10-secochola-5,7,10(19)-trien-24-one

(7E)-(1R,3R,24aR)-24a-fluoro-24a-(thiazole-2-yl)-24a-homo-19-nor-9,10-secochola-5,7-diene-1,3-diol

(7E)-(1R,3R,24aS)-24a-fluoro-24a-(thiazole-2-yl)-24a-homo-19-nor-9,10-secochola-5,7-diene-1,3-diol

(5Z,7E)-(1S,3R,24aR)-24a-fluoro-24a-(thiazole-2-yl)-24a-homo-9,10-secochola-5,7,10(19)-triene-1,3-diol

(5Z,7E)-(1S,3R,24aS)-24a-fluoro-24a-(thiazole-2-yl)-24a-homo-9,10-secochola-5,7,10(19)-triene-1,3-diol

(7E)-(1R,3R,24aR)-24a-(acetyloxy)-24a-(thiazole-2-yl)-24a-homo-19-nor-9,10-secochola-5,7-diene-1,3,24a-triol

(7E)-(1R,3R,24aS)-24a-(acetyloxy)-24a-(thiazole-2-yl)-24a-homo-19-nor-9,10-secochola-5,7-diene-1,3,24a-triol

(7E)-(1R,3R,24aR)-24a-(2,2-dimethylpropanoyloxy)-24a-(thiazole-2-yl)-24a-homo-19-nor-9,10-secochola-5,7-diene-1,3,24a-triol

(7E)-(1R,3R,24aS)-24a-(2,2-dimethylpropanoyloxy)-24a-(thiazole-2-yl)-24a-homo-19-nor-9,10-secochola-5,7-diene-1,3,24a-triol and

(7E)-(1R,3R)-2-bromo-24a-(thiazole-2-yl)-24a-homo-19-nor-9,10-secochola-5,7-diene-1,3,24a-triol.

5. A process for production of a compound according to claim 1, in which Q is C₂–

C₅ alkyl, said process comprising;

converting a compound of formula III

6. A pharmaceutical preparations comprising at least one compound according to claim 1 and a pharmaceutically compatible adjuvant or vehicle.

7. A compound according to claim 1, wherein —

C(O)R₅ is derived from formic acid, acetic acid, propionic acid, butanoic acid, pentanoic acid or pivalic acid can be mentioned.

8. A compound according to claim 1, wherein Y₁ and Y₂, independently of one another, are each hydrogen, acetyl, propionyl or pivaloyl.

9. A compound according to claim 1, wherein Y₃ is hydrogen, fluorine, chlorine, bromine, hydroxy ,OR₅ or —

OC(O)R₅.

10. A compound according to claim 1, wherein Y₃ methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, or t-butoxy.

11. A compound according to claim 1, wherein R₃ and R₄, independently of one another, are each fluorine, chlorine, bromine atom, or alkyl with 1 to 4 carbon atoms, or together are a methylene group or together with quaternary carbon atom 20 are a 3- to 7-membered, saturated or unsaturated carbocyclic ring.

12. A compound according to claim 1, wherein R₃ is H, and R₄ is methyl;

R₃ is methyl, and R₄ is H;

R₃ and R₄ are each methyl;

R₃ and R₄ together form a methylene group;

or R₃ and R₄ together with tertiary carbon atom 20 form a cyclopropyl ring.

13. A compound according to claim 1, wherein R₅ is methyl, ethyl, propyl, i-propyl, butyl or phenyl.

14. A compound according to claim 1, wherein R₅ is derived from a C₁ to C₉ alkanecarboxylic acid.

15. A compound according to claim 1, wherein R₆ is methyl, ethyl, propyl, butyl, isobutyl, tert-butyl, pentyl, isopentyl, neopentyl or hexyl.

16. A compound according to claim 1, wherein R₆ is benzyl or phenyl which is unsubstituted or substituted by one or more halogen atom(s), hydroxy group(s), C₁–

C₄ alkoxy group(s), CF₃ group(s) or amino group(s).

17. A compound according to claim 1, wherein Q is methylene, ethylene or propylene.

18. A compound according to claim 1, wherein X₁ and X₂ together are a carbonyl group, or

X₁ is hydroxyl or fluorine and X₂ is hydrogen, or

X₁ is hydrogen X₂ is hydroxyl or fluorine, or

X₁ is —

OC(O)R₆ and X₂ is hydrogen, or

X₁is hydrogen and X₂ is —

OC(O)R₆.

19. A compound according to claim 1, wherein Z is a oxazole or thiazole ring, which can carry one or more methyl, ethyl or propyl groups at any position(s), which in turn can be substituted by halogen.

20. A compound according to claim 1, wherein Z is a benzoxazole or benzothiazole ring, which can carry methyl, ethyl or propyl groups at any position, which in turn can be substituted by halogen.

21. A compound according to claim 1, wherein said compound is selected from:

(7E)-(1R,3R,24aR)-24a-(oxazole-4-yl)-24a-homo-19-nor-9,10-secochola-5,7-diene-1,3,24a-triol,

(7E)-(1R,3R,24aS)-24a-(oxazole-4-yl)-24a-homo-19-nor-9,10-secochola-5,7-diene-1,3,24a-triol,

(5Z,7E)-(1S,3R,24aR)-24a-(oxazole-4-yl)-24a-homo-9,10-secochola-5,7,10(19)-triene-1,3,24a-triol,

(5Z,7E)-(1S,3R,24aS)-24a-(oxazole-4-yl)-24a-homo-9,10-secochola-5,7,10(19)-triene-1,3,24a-triol,

(7E)-(1R,3R,20S,24aR)-24a-(oxazole-4-yl)-24a-homo-19-nor-9,10-secochola-5,7-diene-1,3,24a-triol,

(7E)-(1R,3R,20S,24aS)-24a-(oxazole-4-yl)-24-a-homo-19-nor-9,10-secochola-5,7-diene-1,3,24a-triol,

(7E)-(1R,3R,20S)-1,3-dihydroxy-24a-(oxazole-4-yl)-24-a-homo-19-nor-9,10-secochola-5,7-dien-24a-one,

(5Z,7E)-(1S,3R,20S,24aR)-24a-(oxazole-4-yl)-24a-homo-9,10-secochola-5,7,10(19)-triene-1,3,24a-triol,

(5Z,7E)-(1S,3R,20S,24aS)-24a-(oxazole-4-yl)-24a-homo-9,10-secochola-5,7,10(19)-triene-1,3,24a-triol,

(5Z,7E)-(1S,3R,20S)-1,3-dihydroxy-24a-(oxazole-4-yl)-24a-homo-9,10-secochola-5,7,10(19)-trien-24a-one,

(5Z,7E)-(1S,3R24R)-24-(oxazole-4-yl)-9,10-secochola-5,7,10(19)-triene-1,3,24a-triol,

(5Z,7E)-(1 S,3R,24S)-24-(oxazole-4-yl)-9,10-secochola-5,7,10(19)-triene-1,3,24a-triol, and

(5Z,7E)-(1S,3R)-1,3-dihydroxy-24-(oxazole-4-yl)-9,10-secochola-5,7,10(19)-trien-24-one.

22. A compound according to claim 1, wherein said compound is selected from:

(7E)-(1R,3R,24aR)-24a-(thiazole-2-yl)-24a-homo-19-nor-9,10-secochola-5,7-diene-1,3,24a-triol,

(7E)-(1R,3R,24aS)-24a-(thiazole-2-yl)-24a-homo-19-nor-9,10-secochola-5,7-diene-1,3,24a-triol,

(7E)-(1R,3R)-1,3-dihydroxy-24a-(thiazole-2-yl)-24-a-homo-19-nor-9,10-secochola-5,7-dien-24a-one,

(5Z,7E)-(1S,3R,24aR)-24a-(thiazole-2-yl)-24a-homo-9,10-secochola-5,7,10(19)-triene-1,3,24a-triol,

(5Z,7E)-(1S,3R,24aS)-24a-(thiazole-2-yl)-24a-homo-9,10-secochola-5,7,10(19)-triene-1,3,24a-triol,

(5Z,7E)-(1S,3R)-1,3-dihydroxy-24a-(thiazole-2-yl)-24a-homo-9,10-secochola-5,7,10(19)-trien-24a-one,

(7E)-(1R,3R,24aR)-24a-(4-methylthiazole-2-yl)-24a-homo-19-nor-9,10-secochola-5,7-diene-1,3,24a-triol,

(7E)-(1R,3R,24aS)-24a-(4-methylthiazole-2-yl)-24a-homo-19-nor-9,10-secochola-5,7-diene-1,3,24a-triol,

(7E)-(1R,3R)-1,3-dihydroxy-24a-(4-methylthiazole-2-yl)-24a-homo-19-nor-9,10-secochola-5,7-dien-24a-one,

(5Z,7E)-(1S,3R,24aR)-24a-(4-methylthiazole-2-yl)-24a-homo-9,10-secochola-5,7,10(19)-triene-1,3,24a-triol,

(5Z,7E)-(1,3R,24aS)-24a-(4-methylthiazole-2-yl)-24a-homo-9,10-secochola-5,7,10(19)-triene-1,3,24a-triol,

(5Z,7E)-(1S,3R)-1,3-dihydroxy-24a-(4-methylthiazole-2-yl)-24a-homo-9,10-secochola-5,7,10(19)-trien-24a-one,

(7E)-(1R3R,24aR)-24a-[5-(2-hydroxyethyl)-4-methylthiazole-2-yl]-24a-homo-19-nor-9,10-secochola-5,7-diene-1,3,24a-triol,

(7E)-(1R,3R,24aS)-24a-[5-(2-hydroxyethyl)-4-methylthiazole-2-yl]-24a-homo-19-nor-9,10-secochola-5,7-diene-1,3,24a-triol,

(7E)-(1R,3R)-1,3-dihydroxy-24a-[5-(2-hydroxyethyl)-4-methylthiazole-2-yl]-24a-homo-19-nor-9,10-secochola-5,7-dien-24a-one,

(7E)-(1R,3R,20S,24aR)-24a-(thiazole-2-yl)-24a-homo-19-nor-9,10-secochola-5,7-diene-1,3,24a-triol,

(7E)-(1R,3R,20S,24aS)-24a-(thiazole-2-yl)-24-a-homo-19-nor-9,10-secochola-5,7-diene-1,3,24a-triol,

(7E)-(1R,3R,20S)-1,3-dihydroxy-24a-(thiazole-2-yl)-24-a-homo-19-nor-9,10-secochola-5,7-dien-24a-one,

(5Z,7E)-(1S,3R,20S,24aR)-24a-(thiazole-2-yl)-24a-homo-9,10-secochola-5,7,10(19)-triene-1,3,24a-triol,

(5Z,7E)-(1S,3R,20S,24aS)-24a-(thiazole-2-yl)-24a-homo-9,10-secochola-5,7,10(19)-triene-1,3,24a-triol,

(5Z,7E)-(1S,3R,20S)-1,3-dihydroxy-24a-(thiazole-2-yl)-24a-homo-9,10-secochola-5,7,10(19)-trien-24a-one,

(5Z,7E)-(1S,3R,24S)-24-(thiazole-2-yl)-9,10-secochola-5,7,10(19)-triene-1,3,24-triol,

(5Z,7E)-(1S,3R,24R)-24-(thiazole-2-yl)-9,10-secochola-5,7,10(19)-triene-1,3,24-triol,

(5Z,7E)-(1S,3R)-1,3-dihydroxy-24-(thiazole-2-yl)-9,10-secochola-5,7,10(19)-trien-24-one,

(7E)-(1R,3R,20S,24aR)-24a-(4-methylthiazole-2-yl)-24a-homo-19-nor-9,10-secochola-5,7-diene-1,3,24a-triol,

(7E)-(1R,3R,20S,24aS)-24a-(4-methylthiazole-2yl)24a-homo 19-nor-9,10-secochola-5,7-diene-1,3,24a-triol,

(7E)-(1R,3R,20S)-1,3-dihydroxy-24a-(4-methylthiazole-2-yl)-24-a-homo-19-nor-9,10-secochola-5,7-dien-24a-one,

(5Z,7E)-(1S,3R,20S,24aR)-24a-(4-methylthiazole-2-yl)-24a-homo-9,10-secochola-5,7,10(19)-triene-1,3,24a-triol,

(5Z,7E)-(1S,3R,20S,24aS)-24a-(4-methylthiazole-2-yl)-24a-homo-9,10-secochola-5,7,10(19)-triene-1,3,24a-triol,

(5Z,7E)-(1S,3R,20S)-1,3-dihydroxy-24a-(4-methylthiazole-2-yl)-24a-homo-9,10-secochola-5,7,10(19)-trien-24a-one,

(5Z,7E)-(1S,3R,24R)-24-(4-methylthiazole-2-yl)-9,10-secochola-5,7,10(19)-triene-1,3,24a-triol,

(5Z,7E)-(1S,3R,24S)-24-(4-methylthiazole-2-yl)-9,10-secochola-5,7,10(19)-triene-1,3,24a-triol,

(5Z,7E)-(1S,3R)-1,3-dihydroxy-24-(4-methylthiazole-2-yl)-9,10-secochola-5,7,10(19)-trien-24-one,

(5Z,7E)-(1S,3R,24S)-24-(4-methylthiazole-2-yl)-9,10-secochola-5,7,10(19)-triene-1,3,24-triol,

(5Z,7E)-(1S,3R,24R)-24-(4-methylthiazole-2-yl)-9,10-secochola-5,7,10(19)-triene-1,3,24-triol,

(5Z,7E)-(1S,3R)-1,3-dihydroxy-24-(4-methylthiazole-2-yl)-9,10-secochola-5,7,10(19)-trien-24-one,

(7E)-(1R,3R24aR)-24a-fluoro-24a-(thiazole-2-yl)-24a-homo-19-nor-9,10-secochola-5,7-diene-1,3-diol,

(7E)-(1R,3R,24aS)-24a-fluoro-24a-(thiazole-2-yl)-24a-homo-19-nor-9,10-secochola-5,7-diene-1,3-diol,

(5Z,7E)-(1S,3R,24aR)-24a-fluoro-24a-(thiazole-2-yl)-24a-homo-9,10-secochola-5,7,10(19)-triene-1,3-diol,

(5Z,7E)-(1S,3R,24aS)-24a-fluoro-24a-(thiazole-2-yl)-24a-homo-9,10-secochola-5,7,10(19)-triene-1,3-diol,

(7E)-(1R,3R,24aR)-24a-(acetyloxy)-24a-(thiazole-2-yl)-24a-homo-19-nor-9,10-secochola-5,7-diene-1,3,24a-triol,

(7E)-(1R,3R,24aS)-24a-(acetyloxy)-24a-(thiazole-2-yl)-24a-homo-19-nor-9,10-secochola-5,7-diene-1,3,24a-triol,

(7E)-(1R,3R,24aR)-24a-(2,2-dimethylpropanoyloxy)-24a-(thiazole-2-yl)-24a-homo-19-nor-9,10-secochola-5,7-diene-1,3,24a-triol,

(7E)-(1R,3R,24aS)-24a-(2,2-dimethylpropanoyloxy)-24a-(thiazole-2-yl)-24a-homo-19-nor-9,10-secochola-5,7-diene-1,3,24a-triol, and

(7E)-(1R,3R)-2-bromo-24a-(thiazole-2-yl)-24a-homo-19-nor-9,10-secochola-5,7-diene-1,3,24a-triol.

23. A compound according to claim 1, wherein said compound is selected from:

(7E)-(1R,3R,24aR)-24a-(benzothiazole-2-yl)-24a-homo-19-nor-9,10-secochola-5,7-diene-1,3,24a-triol,

(7E)-(1R,3R,24aS)-24a-(benzothiazole-2-yl)-24a-homo-19-nor-9,10-secochola-5,7-diene-1,3,24a-triol, and

(7E)-(1R,3R)-24a-(benzothiazole-2-yl)-1,3-dihydroxy-24a-homo-19-nor-9,10-secochola-5,7-dien-24a-one.

24. A compound according to claim 1, wherein said compound is selected from:

(7E)-(1R,3R,2aR)-24a-(oxazol-4-yl)-24a-homo-19-nor-9,10-secochola-5,7-diene-1,3,24a-triol,

(5Z,7E)-(1S,3R,24aR)-24a-(oxazol-4-yl)-24a-homo-9,10-secochola-5,7,10(19)-triene-1,3,24a-triol, and

(5Z,7E)-(1S,3R,24R)-24-(thiazol-2-yl)-9,10-secochola-5,7,10(19)-triene-1,3,24a-triol.

25. A compound according to claim 1, wherein R₁ and R₂ together are methylene, Y₃is H, and Z is a thiazole group which is unsubstituted or substituted by one or more fluorine, chlorine, bromine or iodine atoms, one or more hydroxy groups, one or more COOR₆ groups, and/or one or more C₁–

C₅ alkyl groups, which in turn can be substituted by one or more fluorine, chlorine, bromine or iodine atoms, C₁–

C₆ alkoxy groups and/or COOR₆ groups.

26. A compound according to claim 1, wherein Z is oxazolyl which is unsubstituted or substituted by one or more fluorine, chlorine, bromine or iodine atoms, one or more hydroxy groups, one or more COOR₆ groups, and/or one or more C₁–

C₅ alkyl groups, which in turn can be substituted by one or more fluorine, chlorine, bromine or iodine atoms, C₁–

C₆ alkoxy groups and/or COOR₆ groups.

27. A compound according to claim 1, wherein Z is thiazolyl which is unsubstituted or substituted by one or more fluorine, chlorine, bromine or iodine atoms, one or more hydroxy groups, one or more COOR₆ groups, and/or one or more C₁–

C₅ alkyl groups, which in turn can be substituted by one or more fluorine, chlorine, bromine or iodine atoms, C₁–

C₆ alkoxy groups and/or COOR₆ groups.

28. A compound according to claim 1, wherein Z is benzothiazolyl which is unsubstituted or substituted by one or more fluorine, chlorine, bromine or iodine atoms, one or more hydroxy groups, one or more COOR₆ groups, and/or one or more C₁–

C₅ alkyl groups, which in turn can be substituted by one or more fluorine, chlorine, bromine or iodine atoms, C₁–

C₆ alkoxy groups and/or COOR₆ groups.

29. A compound according to claim 1, wherein Z is benzoxazolyl which is unsubstituted or substituted by one or more fluorine, chlorine, bromine or iodine atoms, one or more hydroxy groups, one or more COOR₆ groups, and/or one or more C₁–

C₅ alkyl groups, which in turn can be substituted by one or more fluorine, chlorine, bromine or iodine atoms, C₁–

C₆ alkoxy groups and/or COOR₆ groups.

30. A compound according to claim 27, wherein R₁ and R₂ together are methylene.

31. A compound according to claim 27, wherein Y₃ is H.